Characterisation and aerosolisation of mannitol particles produced via confined liquid impinging jets

Mannitol particles, produced by spray drying (SD), have been used commercially (Aridol™) in bronchial provocation test. In this study, we propose an alternative method to produce inhalable mannitol powders. The elongated mannitol particles (number median length 4.0 μm, and axial ratio of 3.5) were prepared using a confined liquid impinging jets (CLIJs) followed by jet milling (JM). Spray dried and jet milled raw mannitol particles were compared in an attempt to assess the performance of the particles produced by the new method. Aerosol performance of the three different powders (CLIJ, SD, and JM) was relatively poor (fine particle fraction or FPF_loaded below 15%) when dispersed by the Rotahaler^®. Dispersion through the Aeroliser^® led to better aerosol performance of the CLIJ mannitol (FPF_loaded 20.3%), which is worse than the JM (FPF_loaded 30.3%) and SD mannitol particles (FPF_loaded 45.7%) at 60 L/min, but comparable (FPF_loaded 40.0%) with those of the JM (FPF_loaded 40.7%) and SD (FPF_loaded 45.5%) powders at 100 L/min. Hence, the optimum use of these elongated mannitol particles can be achieved at increased air flow with a more efficient inhaler. In addition to crystallinity, morphology, and particle size distribution, the surface energies of these powders were measured to explain the differences in aerosol performance. A major advantage of using the CLIJ method is that it can be scaled up with a good yield as the precipitate can be largely collected and recovered on a filter, compared with spray drying which has a low collection efficiency for fine particles below 2 μm.